Project Summary. This revised K01 application will provide specialized training in cognitive neuroscience that utilizes functional magnetic resonance imaging (fMRI) as a research tool. Cognitive experimental tasks, brain regions of interest (ROIs) and multiple brain connectivity data analysis approaches will be used to understand neural mechanisms that underlie implicit and explicit memory processes that impart risk for problematic drug use behavior in youthful samples who vary in cocaine exposure, and how these mechanisms are affected by cognitive manipulations. The training and research plans will directly advance the candidate's goal of developing an independent line of transdisciplinary research that investigates spreading of activation in semantic memory for appetitive stimuli that links the processes of memory and craving, and supports persistence of chronic cocaine use in humans. Brain areas related to memory and craving and connectivity between memory and craving related brain areas will be examined during the performance of implicit and explicit memory tasks that will include cocaine and neutral picture cues. The areas of career development include (1) formal training in the theory and application of functional neuroimaging using fMRI;(2) formal training in neurobiology of substance abuse, and expanding candidate's prior training in cognitive neuroscience;(3) developing a background in bioinformatics needed to conduct functional imaging data analyses;and (4) integrating fMRI as a tool, cognitive neuroscience, and addictions research. These goals will be accomplished through coursework, workshops, seminars, and conferences and through extensive one-on- one as well as collective mentoring and consulting with investigators whose research is directly relevant to the goals of this application. The candidate's institutional environment provides strong support to accomplish these goals. In Experiment 1, individuals at high- vs. low-risk for developing cocaine use disorder and those who are chronic cocaine smokers will take part in an implicit semantic priming paradigm that will include a study phase and a picture/non-picture decision test;and an explicit picture recognition task. During the explicit recognition task, participants will decide whether a particular stimulus seen on the screen was presented during the study phase. Established memory and craving related brain ROIs and connectivity between memory and craving related ROIs will be examined during these tasks. In Experiment 2, at-risk and chronic cocaine smokers'neurocognitive mechanisms will be examined using the same tasks, except that they will also perform an additional attention demanding task during the study phase. Brain ROIs and connectivity analyses will be used to reveal the underlying neural substrates involved in the restricted activation in semantic memory. Knowledge gained from this research can be used ultimately to build a more nuanced perspective of 'neurocognitive influences'that can be used to tailor addiction treatment intervention strategies to individual needs, better predict treatment outcome, and develop more targeted pharmacotherapies. PUBLIC HEALTH RELEVANCE: Relevance. This application applies cutting-edge fMRI techniques and is the first study to examine neural mechanisms that underlie implicit and explicit memory processes for cocaine-related stimuli in individuals who vary in cocaine exposure. Brain areas related to memory and craving and connectivity between memory and craving related brain areas will be explored while individuals perform implicit and explicit memory tasks involving cocaine and neutral picture cues. This approach to understanding neural and cognitive influences that underlie risk for addiction and characterize chronic cocaine users will contribute to the candidate's ability to conduct research on the integrated operation of the autonomic nervous and neural systems, which constitute a multi-system vulnerability to substance addiction, and will be useful for clinicians seeking to make prevention and treatment programs more effective.